1. Field of the Invention
The present invention relates to a process for preparing Estracyt compounds having a carcinostatic bound thereto, useful in the treatment of prostatic cancer.
2. Description of the Prior Art
Studies on hormone-dependent cancers have been considerable adavnce in recent years and one approach that is considered effective is transporting a high concentration of a hormone-based carcinostatic to a specific site in the cancer tissues and letting the carcinostatic exhibit its cancer control activity at that site. Estracyt.RTM. is the trademark for estradiol-3N-bis(2-chloroethyl)-carbamate-17.beta.-phosphate that Ab-Leo A.G., Sweden developed in 1966 for achieving this purpose. Estracyt.RTM. has the following formula (I): ##STR1##
Estracyt.RTM. is a substance wherein estradiol-17.beta.-phosphate of formula (II) has a carbamate bonding of nitrogen mustard of formula (III) at 3-position: ##STR2##
Two derivatives having the same activity as Estracyt.RTM. are estramustine of formula (IV) and estromustine of formula (V): ##STR3##
It has been reported that Estracyt.RTM., estramustine and estromustine (hereunder collectively referred to as "Estracyt compounds"), when administered into the human body, are specifically accumulated in prostatic organs (e.g. dorsal prostate, DP; dorsolateral prostate, DLP; and seminal vesicle, SV) (see, for example, H. Yamanaka, K. Kitaura, K. Imai, H. Yuasa, K. Nakai, Y. Matsumura, H. Uehara and K. Shiba, "In Vivo Studies of .sup.3 H-estramustine in Castrated Male Rat", Acta Urol. Jap., 27, 243-250, 1981). It has also been reported that these Estracyt compounds are very effective in controlling progressive prostatic cancer.
Estracyt compounds may function as estrogen-cancer control agent complexes but their cancer control activities are not completely satisfactory.